Selective neuronal degeneration induced by soluble oligomeric amyloid beta-protein

被引:190
作者
Kim, HJ
Chae, SC
Lee, DK
Chromy, B
Lee, SC
Park, YC
Klein, WL
Krafft, GA
Hong, ST
机构
[1] Chonbuk Natl Univ, Inst Cardiovasc Res, Sch Med, Chonju 561712, South Korea
[2] Chonbuk Natl Univ, Dept Microbiol, Sch Med, Chonju 561712, South Korea
[3] Jinis Biopharmacceut Co, Div Res, Chonju, South Korea
[4] Wonkwang Univ, Sch Med, Genom Res Ctr Immune Disorder, Iksan, Chonbuk, South Korea
[5] Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA
[6] Hanlyo Univ, Dept Adv Mat Engn, Kwangyang, Chonnam, South Korea
[7] HumanBio Co, Res Ctr Biotechnol Human, Iksan, Chonbuk, South Korea
[8] Evanston NW Healthcare Res Inst, Evanston, IL 60201 USA
关键词
Alzheimer's disease; regiospecific; slice cultures; hippocampal CA1;
D O I
10.1096/fj.01-0987fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The prevailing amyloid hypothesis for Alzheimer's disease (AD) holds that amyloid beta-protein (Abeta) causes neuronal degeneration by forming neurotoxic fibrillar structures. Yet, many aspects of AD pathology and symptoms are not well explained by this hypothesis. Here, we present evidence that neurotoxicity of soluble oligomeric Abeta closely corresponds to the selective neurodegeneration so distinctly manifest in AD. Selectivity was first observed in vitro, where only the human central nervous system neuronal cells were susceptible to soluble oligomeric Abeta. Furthermore, in mouse cerebral slice treated with soluble oligomeric Abeta, selective regiospecific toxicity was evident in the hippocampal CA1, a division important for memory, but not in the CA3 subfield. The fibrillar Abeta, however, killed neurons in all regions of the cerebral slice cultures and also in cerebellar slices. Remarkably, even at the highest soluble oligomeric Abeta concentrations, cerebellar neurons were completely spared, consistent with one of the hallmark features of AD pathology. Our observation of the selective neurodegeneration of soluble oligomeric Abeta to neurons involved in cognitive function may provide a new opportunity for the development of an effective AD therapy as well as elucidating the pathological mechanism of AD.
引用
收藏
页码:118 / +
页数:18
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